The different clonal origins of metachronous and synchronous metastases

Ofer N. Gofrit*, Ben Gofrit, Yuval Roditi, Aron Popovtzer, Steve Frank, Jacob Sosna, Marina Orevi, S. Nahum Goldberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Metastases are the leading cause of mortality in cancer patients. Linear and parallel are the two prominent models of metastatic progression. Metastases can be detected synchronously along with the primary tumor or metachronously, following treatment of localized disease. The aim of the study was to determine whether synchronous metastases (SM) and metachronous metastases (MM) differ only in lead-time or stem from different biological processes. Materials and methods: We retrospectively studied the chest CTs of 791 patients inflicted by eleven malignancy types that were treated in our institution in the years 2010–2020. Patient’s population included 396 with SM and 395 with MM. The diameter of 15,427 lung metastases was measured. Clonal origin was deduced from the linear/parallel ratio (LPR)-a computerized analysis of metastases diameters. LPR of 1 suggests pure linear dissemination and − 1 pure parallel. Results: Patients with MM were significantly older (average of 62.9 vs 60.7 years, p = 0.02), and higher percentage of them were males (58.7% vs 51.1%, p = 0.03). Median overall survival of patients with MM and SM was remarkably similar (23 months and 26 months respectively, p = 0.774) when calculated from the time of metastases diagnosis. Parallel dissemination (LPR ≤ 0) was found in 35.4% of patients with MM compared to only 19.8% of the patients with SM (p < 0.00001). Conclusion: Patients with SM and MM differ in demography and in clonal origin. Different therapeutic approaches may be considered in these two conditions.

Original languageAmerican English
Pages (from-to)11085-11092
Number of pages8
JournalJournal of Cancer Research and Clinical Oncology
Issue number13
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).


  • Clonal origin
  • Linear
  • Metachronous metastases
  • Parallel ratio
  • Synchronous metastases


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